Project Summary/Abstract This shared instrumentation grant application, from the Light Microscope Imaging Facility at Case Western Reserve University (CWRU), is for funds for a new point-scanning Leica SP8 confocal microscope. Currently the Facility has three point-scanning confocal microscopes available. However, two of the three have reached the end of usage due to breakdowns, discontinuation of service contracts by vendors, and difficulties of obtaining repair parts. The one remaining confocal will not be able to support the labs currently using confocal technology at CWRU if these aging confocals stop functioning altogether. In order to continue to support the ongoing NIH funded research that relies on confocal instrumentation, we need to replace the two failing instruments with one new one that can offer multi-channel high resolution 3D imaging, low signal detection, live cell imaging, and flexibility in channel setup to enable the use of many different fluorophores combinations for multi-color colocalization experiments. There have been major innovations in the past few years in both detector and super-resolution technology and we have configured the requested system to take advantage of these improvements in detection, contrast and resolution and expand to super-resolution 3D analysis. The instrument will be housed in a well-established shared core facility that supports NIH-funded investigators by giving them access to state-of-the-art microscopy technologies that enhance collaborative, multidisciplinary research. The principal investigators who will initially benefit from this system work on a broad range of organisms, basic research and health-related issues, including the fundamental molecular mechanisms that underlie division (deBoer), movement (Ritzmann), infection (Wearsch), differentiation (Tesar), trafficking (Park, Wearsch), neuronal development (Broihier, Chen), 3D organization (all projects), and diseases such as cancer (Exner, Taylor), vision & hearing loss (Park, Gopal, McDermott, Stepanyan), multiple sclerosis (Adams, Tesar) as well as to pave the way for nanoscale therapies in the detection and treatment of said diseases (Exner, Adams, Tesar). Other laboratories that already use the Imaging Facility are also anticipated to take advantage of this new technology. Without this new instrumentation, the research projects of many of our investigators will not be possible; those investigators who want to expand their research into new areas to include these advanced sub-diffraction capabilities will also be thwarted. As configured, this instrumentation is essential to our evolving research, clinical and translational programs and will allow our core facility to continue to provide state-of-the-art imaging to our expanding user base.